Large scale genotyping study for asthma in the Japanese population.
Large scale genotyping study for asthma in the Japanese population.
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DOI：
10.1186/1756-0500-2-54
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发表时间：
2009-03-31
影响因子：
1.8
通讯作者：
Noguchi, Emiko
中科院分区：
文献类型：
--
作者：
Imada, Yoshiko;Fujimoto, Masaya;Noguchi, Emiko
背景：哮喘是一种复杂的表型，受遗传和环境因素的影响。已经进行了全基因组连锁和关联研究，以确定哮喘的易感基因。这些研究发现了与这种疾病有关的新基因和途径，其中许多是以前未知的。目的：开展一项大规模基因分型研究，以确定日本人群中的哮喘易感基因。方法：我们对288名特应性哮喘患者和1032名对照者进行了一项大规模的三阶段关联研究，采用多重PCR-Invader检测方法，检测82935个单核苷酸多态性（snp）（第一阶段）。在哮喘家族（216个家族，762名成员，第二阶段）、541名独立患者和744名对照（第三阶段）的样本中进一步对与哮喘强烈相关的snp进行基因分型。结果：PEX19 (rs2820421) 5′区snp在1 ~ 3期分析中显著相关（P < 0.05）；但P值未达到统计学显著水平（合并P = 3.8 × 10-5；经Bonferroni校正P = 6.57 × 10-7）。在第一和第二阶段分析中，HPCAL1 （rs3771140）和IL18R1 （rs3213733）上的snp与哮喘相关，但在第三阶段分析中未观察到这种关联。结论：没有关联达到全基因组意义，但出现了几个可能的关联位点。为了预防和治疗哮喘，需要进一步的研究来验证这些结果。
BACKGROUND: Asthma is a complex phenotype that is influenced by both genetic and environmental factors. Genome-wide linkage and association studies have been performed to identify susceptibility genes for asthma. These studies identified new genes and pathways implicated in this disease, many of which were previously unknown.OBJECTIVE: To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population.METHODS: We performed a large-scale, three-stage association study on 288 atopic asthmatics and 1032 controls, by using multiplex PCR-Invader assay methods at 82,935 single nucleotide polymorphisms (SNPs) (1st stage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2nd stage), 541 independent patients, and 744 controls (3rd stage).RESULTS: SNPs located in the 5' region of PEX19 (rs2820421) were significantly associated with P < 0.05 through the 1st to the 3rd stage analyses; however, the P values did not reach statistically significant levels (combined, P = 3.8 x 10-5; statistically significant levels with Bonferroni correction, P = 6.57 x 10-7). SNPs on HPCAL1 (rs3771140) and on IL18R1 (rs3213733) were associated with asthma in the 1st and 2nd stage analyses, but the associations were not observed in the 3rd stage analysis.CONCLUSION: No association attained genome-wide significance, but several loci for possible association emerged. Future studies are required to validate these results for the prevention and treatment of asthma.